Cis-4-5-didehydro-13,14-didehydro-11-deoxy-PGE1 compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit protaglandin-like activity, and are accordingly useful for the same pharamcologicl purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,740,filed Feb. 13, 1976, now pending issuance as a United States Patent.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from Ser. No. 820,974, filed Aug. 1, 1977, now U.S. Pat.No. 4,099,015, issued July 4, 1978, which is a divisional application ofSer. No. 657,740.

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is##STR2## wherein Z₄ is cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --, wherein gis one, 2, or 3;Wherein R₇ is --(CH₂)_(m) --CH₃, wherein m is one to 5,inclusive; Wherein L₁ is ##STR3## or a mixture of ##STR4## wherein R₃and R₄ are hydrogen, methyl, or fluoro, being the same or different,with the proviso that one of R₃ and R₄ is methyl only when the other ishydrogen or methyl; wherein M₁ is ##STR5## wherein R₅ and R₆ arehydrogen or methyl, with the proviso that one of R₅ and R₆ is methylonly when the other is hydrogen; and Wherein R₁ is hydrogen, alkyl ofone to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms,inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenylsubstituted with one, two, or three chloro or alkyl of one to 3 carbonatoms, inclusive, or a pharmacologically acceptable cation.
 2. Acompound according to claim 1, wherein D is ##STR6##
 3. A compoundaccording to claim 2, wherein M₁ is ##STR7##
 4. A compound according toclaim 3, wherein g is one.
 5. A compound according to claim 4, whereinR₃, R₄, R₅, and R₆ are all hydrogen. 6.15-epi-cis-4,5-Didehydro-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methylester, a compound according to claim
 4. 7. A compound according to claim2, wherein M₁ is ##STR8##
 8. A compound according to claim 7, wherein gis three.
 9. A compound according to claim 7, wherein g is one.
 10. Acompound according to claim 9, wherein R₃ and R₄ are both hydrogen. 11.A compound according to claim 10, wherein R₅ is methyl. 12.Cis-4,5-Didehydro-15-methyl-13,14-didehydro-8β,12.alpha.-11-deoxy-PGE₁,a compound according to claim
 11. 13.Cis-4,5-Didehydro-15-methyl-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methylester, a compound according to claim
 11. 14. A compound according toclaim 10, wherein R₆ is methyl. 15.Cis-4,5-Didehydro-13,14-didehydro-8β,12α-11-deoxy-PGE₁, 15-methyl ether,a compound according to claim
 14. 16.Cis-4,5-Didehydro-13,14-didehydro-8β,12α-11-deoxy-PGE_(l) , methylester, 15-methyl ether, a compound according to claim
 14. 17. A compoundaccording to claim 10, wherein R₅ and R₆ are both hydrogen. 18.Cis-4,5-Didehydro-13,14-didehydro-8β,12α-11-deoxy-PGE₁, a compoundaccording to claim
 17. 19.Cis-4,5-Didehydro-13,14-didehydro-8β12α-11-deoxy-PGE₁, methyl ester, acompound according to claim
 17. 20. A compound according to claim 9,wherein at least one of R₃ and R₄ is methyl.
 21. A compound according toclaim 20, wherein R₃ and R₄ are both methyl.
 22. A compound according toclaim 21, wherein R₅ is methyl. 23.Cis-4,5-Didehydro-15,16,16-trimethyl-13,14-didehydro-8β,12α-11-deoxy-PGE₁,methyl ester, a compound according to claim
 22. 24. A compound accordingto claim 21, wherein R₆ is methyl. 25.Cis-4,5-Didehydro-16,16-dimethyl-13,14-didehydro-8β,12.alpha.-11-deoxy-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 24. 26. Acompound according to claim 21, wherein R₅ and R₆ are both hydrogen. 27.Cis-4,5-Didehydro-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-PGE.sub.1,a compound according to claim
 26. 28.Cis-4,5-Didehydro-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-PGE₁,methyl ester, a compound according to claim
 26. 29. A compound accordingto claim 9, wherein at least one of R₃ and R₄ is fluoro.
 30. A compoundaccording to claim 29, wherein R₃ and R₄ are both fluoro.
 31. A compoundaccording to claim 30, wherein R₅ is methyl. 32.Cis-4,5-Didehydro-15-methyl-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-PGE₁,methyl ester, a compound according to claim
 31. 33. A compound accordingto claim 30, wherein R₆ is methyl. 34.Cis-4,5-Didehydro-16,16-difluoro-13,14-didehydro-8β,12.alpha.-11-deoxy-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 33. 35. Acompound according to claim 30, wherein R₅ and R₆ are both hydrogen. 36.Cis-4,5-Didehydro-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-PGE.sub.1,a compound according to claim
 35. 37.Cis-4,5-Didehydro-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-PGE₁,methyl ester, a compound according to claim
 35. 38. A compound accordingto claim 1, wherein D is ##STR9##
 39. A compound according to claim 38,wherein M₁ is ##STR10##
 40. A compound according to claim 39, wherein gis one.
 41. A compound according to claim 40, wherein R₃, R₄, R₅, and R₆are all hydrogen. 42.15-epi-cis-4,5-Didehydro-13,14-didehydro-11-deoxy-PGE₁, methyl ester, acompound according to claim
 41. 43. A compound according to claim 38,wherein M₁ is ##STR11##
 44. A compound according to claim 43, wherein gis three.
 45. A compound according to claim 43, wherein g is one.
 46. Acompound according to claim 45, wherein R₃ and R₄ are both hydrogen. 47.A compound according to claim 46, wherein R₅ is methyl. 48.Cis-4,5-Didehydro-15-methyl-13,14-didehydro-11-deoxy-PGE₁, a compoundaccording to claim
 47. 49.Cis-4,5-Didehydro-15-methyl-13,14-didehydro-11-deoxy-PGE₁, methyl ester,a compound according to claim
 47. 50. A compound according to claim 46,wherein R₆ is methyl. 51.Cis-4,5-Didehydro-13,14-didehydro-11-deoxy-PGE₁, 15-methyl ether, acompound according to claim
 50. 52.Cis-4,5-Didehydro-13,14-didehydro-11-deoxy-PGE₁, methyl ester, 15-methylether, a compound according to claim
 50. 53. A compound according toclaim 46, wherein R₅ and R₆ are both hydrogen. 54.Cis-4,5-Didehydro-13,14-didehydro-11-deoxy-PGE₁, a compound according toclaim
 53. 55. Cis-4,5-Didehydro-13,14-didehydro-11-deoxy-PGE₁, methylester, a compound according to claim
 53. 56. A compound according toclaim 45, wherein at least one of R₃ and R₄ is methyl.
 57. A compoundaccording to claim 56, wherein R₃ and R₄ are both methyl.
 58. A compoundaccording to claim 57, wherein R₅ is methyl. 59.Cis-4,5-Didehydro-15,16,16-trimethyl-13,14-didehydro-11-deoxy-PGE₁,methyl ester, a compound according to claim
 58. 60. A compound accordingto claim 57, wherein R₆ is methyl. 61.Cis-4,5-Didehydro-16,16-dimethyl-13,14-didehydro-11-deoxy-PGE₁, methylester, 15-methyl ether, a compound according to claim
 60. 62. A compoundaccording to claim 57, wherein R₅ and R₆ are both hydrogen. 63.Cis-4,5-Didehydro-16,16-dimethyl-13,14-didehydro-11-deoxy-PGE₁, acompound according to claim
 62. 64.Cis-4,5-Didehydro-16,16-dimethyl-13,14-didehydro-11-deoxy-PGE₁, methylester, a compound according to claim
 62. 65. A compound according toclaim 45, wherein at least one of R₃ and R₄ is fluoro.
 66. A compoundaccording to claim 65, wherein R₃ and R₄ are both fluoro.
 67. A compoundaccording to claim 66, wherein R₅ is methyl. 68.Cis-4,5-Didehydro-15-methyl-16,16-difluoro-13,14-didehydro-11-deoxy-PGE₁,methyl ester, a compound according to claim
 67. 69. A compound accordingto claim 66, wherein R₆ is methyl. 70.Cis-4,5-Didehydro-16,16-difluoro-13,14-didehydro-11-deoxy-PGE₁, methylester, 15-methyl ether, a compound according to claim
 69. 71. A compoundaccording to claim 66, wherein R₅ and R₆ are both hydrogen. 72.Cis-4,5-Didehydro-16,16-difluoro-13,14-didehydro-11-deoxy-PGE₁, acompound according to claim
 71. 73.Cis-4,5-Didehydro-16,16-difluoro-13,14-didehydro-11-deoxy-PGE₁, methylester, a compound according to claim 71.